Mathematical model of the cell division cycle of fission yeast.

Much is known about the genes and proteins controlling the cell cycle of fission yeast. Can these molecular components be spun together into a consistent mechanism that accounts for the observed behavior of growth and division in fission yeast cells? To answer this question, we propose a mechanism for the control system, convert it into a set of 14 differential and algebraic equations, study these equations by numerical simulation and bifurcation theory, and compare our results to the physiology of wild-type and mutant cells. In wild-type cells, progress through the cell cycle (G1-->S-->G2-->M) is related to cyclic progression around a hysteresis loop, driven by cell growth and chromosome alignment on the metaphase plate. However, the control system operates much differently in double-mutant cells, wee1(-) cdc25Delta, which are defective in progress through the latter half of the cell cycle (G2 and M phases). These cells exhibit "quantized" cycles (interdivision times clustering around 90, 160, and 230 min). We show that these quantized cycles are associated with a supercritical Hopf bifurcation in the mechanism, when the wee1 and cdc25 genes are disabled. (c) 2001 American Institute of Physics.

[1]  Paul Nurse,et al.  Genetic control of cell size at cell division in yeast , 1975, Nature.

[2]  Tektites and their origins , 1975, Nature.

[3]  P. Fantes Epistatic gene interactions in the control of division in fission yeast , 1979, Nature.

[4]  P. Thuriaux,et al.  Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. , 1980, Genetics.

[5]  D. Koshland,et al.  An amplified sensitivity arising from covalent modification in biological systems. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[6]  L. N. Edmunds Cell cycle clocks , 1984 .

[7]  Paul Russell,et al.  Negative regulation of mitosis by wee1 +, a gene encoding a protein kinase homolog , 1987, Cell.

[8]  Cell Cycle Clocks , 1988 .

[9]  Andrew W. Murray,et al.  The Cell Cycle , 1989 .

[10]  P. Nurse Universal control mechanism regulating onset of M-phase , 1990, Nature.

[11]  Karen Lundgren,et al.  mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2 , 1991, Cell.

[12]  J. Tyson Modeling the cell division cycle: cdc2 and cyclin interactions. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[13]  P. Russell,et al.  The cdc25 M-phase inducer: An unconventional protein phosphatase , 1992, Cell.

[14]  P. Russell,et al.  Pyp3 PTPase acts as a mitotic inducer in fission yeast. , 1992, The EMBO journal.

[15]  John J. Tyson,et al.  Modeling the Cell Division Cycle: M-phase Trigger, Oscillations, and Size Control , 1993 .

[16]  J. Tyson,et al.  Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos. , 1993, Journal of cell science.

[17]  P. Nurse The Wellcome Lecture, 1992. Cell cycle control. , 1993, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[18]  S. Moreno,et al.  Regulation of progression through the Gl phase of the cell cycle by the rum1 + gene , 1994, Nature.

[19]  J. Hayles,et al.  Temporal order of S phase and mitosis in fission yeast is determined by the state of the p34 cdc2 -mitotic B cyclin complex , 1994, Cell.

[20]  Paul Nurse,et al.  p25rum1 orders S phase and mitosis by acting as an inhibitor of the p34cdc2 mitotic kinase , 1995, Cell.

[21]  P. Nurse,et al.  Cyclins of the fission yeast Schizosaccharomyces pombe. , 1995, Seminars in cell biology.

[22]  John J. Tyson,et al.  Quantitative analysis of a molecular model of mitotic control in fission yeast , 1995 .

[23]  K. Nasmyth At the heart of the budding yeast cell cycle. , 1996, Trends in genetics : TIG.

[24]  P. Nurse,et al.  A single fission yeast mitotic cyclin B p34cdc2 kinase promotes both S‐phase and mitosis in the absence of G1 cyclins. , 1996, The EMBO journal.

[25]  S. Moreno,et al.  B‐type cyclins regulate G1 progression in fission yeast in opposition to the p25rum1 cdk inhibitor. , 1996, The EMBO journal.

[26]  K Nasmyth,et al.  Viewpoint: Putting the Cell Cycle in Order , 1996, Science.

[27]  P. Nurse,et al.  A quantitative model for the cdc2 control of S phase and mitosis in fission yeast. , 1996, Trends in genetics : TIG.

[28]  H. Murakami,et al.  A WD repeat protein controls the cell cycle and differentiation by negatively regulating Cdc2/B-type cyclin complexes. , 1997, Molecular biology of the cell.

[29]  J. Tyson,et al.  Modeling the control of DNA replication in fission yeast. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[30]  P. Russell,et al.  Regulation of Schizosaccharomyces pombe Wee1 Tyrosine Kinase* , 1997, The Journal of Biological Chemistry.

[31]  J. Tyson,et al.  Model scenarios for evolution of the eukaryotic cell cycle. , 1998, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[32]  Katherine C. Chen,et al.  Mathematical model of the fission yeast cell cycle with checkpoint controls at the G1/S, G2/M and metaphase/anaphase transitions. , 1998, Biophysical chemistry.

[33]  K. Kitamura,et al.  Fission yeast Ste9, a homolog of Hct1/Cdh1 and Fizzy-related, is a novel negative regulator of cell cycle progression during G1-phase. , 1998, Molecular biology of the cell.

[34]  Kim Nasmyth,et al.  The Polo‐like kinase Cdc5p and the WD‐repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae , 1998, The EMBO journal.

[35]  J. Benito,et al.  Regulation of the G1 phase of the cell cycle by periodic stabilization and degradation of the p25rum1 CDK inhibitor , 1998, The EMBO journal.

[36]  N. Rhind,et al.  Mitotic DNA damage and replication checkpoints in yeast. , 1998, Current opinion in cell biology.

[37]  Tomohiro Matsumoto,et al.  Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. , 1998, Science.

[38]  K. Nasmyth,et al.  Whose end is destruction: cell division and the anaphase-promoting complex. , 1999, Genes & development.

[39]  B. Novák,et al.  Mitotic control in the absence of cdc25 mitotic inducer in fission yeast. , 1999, Journal of cell science.

[40]  K. Kohn Molecular interaction map of the mammalian cell cycle control and DNA repair systems. , 1999, Molecular biology of the cell.

[41]  S. Moreno,et al.  The puc1 cyclin regulates the G1 phase of the fission yeast cell cycle in response to cell size. , 2000, Molecular biology of the cell.

[42]  P. Nurse,et al.  Fission yeast Fizzy‐related protein srw1p is a G1‐specific promoter of mitotic cyclin B degradation , 2000, The EMBO journal.

[43]  J. Tyson,et al.  Modeling the fission yeast cell cycle: quantized cycle times in wee1- cdc25Delta mutant cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Katherine C. Chen,et al.  Kinetic analysis of a molecular model of the budding yeast cell cycle. , 2000, Molecular biology of the cell.

[45]  S. Moreno,et al.  APCste9/srw1 promotes degradation of mitotic cyclins in G1 and is inhibited by cdc2 phosphorylation , 2000, EMBO Journal.